High-content, cell-by-cell assessment of HER2 overexpression and amplification: a tool for intratumoral heterogeneity detection in breast cancer.

Détails

ID Serval
serval:BIB_3B1F249757F4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
High-content, cell-by-cell assessment of HER2 overexpression and amplification: a tool for intratumoral heterogeneity detection in breast cancer.
Périodique
Laboratory investigation; a journal of technical methods and pathology
Auteur(s)
Nguyen H.T., Migliozzi D., Bisig B., de Leval L., Gijs MAM
ISSN
1530-0307 (Electronic)
ISSN-L
0023-6837
Statut éditorial
Publié
Date de publication
05/2019
Peer-reviewed
Oui
Volume
99
Numéro
5
Pages
722-732
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Immunohistochemistry and fluorescence in situ hybridization are the two standard methods for human epidermal growth factor receptor 2 (HER2) assessment. However, they have severe limitations to assess quantitatively intratumoral heterogeneity (ITH) when multiple subclones of tumor cells co-exist. We develop here a high-content, quantitative analysis of breast cancer tissues based on microfluidic experimentation and image processing, to characterize both HER2 protein overexpression and HER2 gene amplification at the cellular level. The technique consists of performing sequential steps on the same tissue slide: an immunofluorescence (IF) assay using a microfluidic protocol, an elution step for removing the IF staining agents, a standard FISH staining protocol, followed by automated quantitative cell-by-cell image processing. Moreover, ITH is accurately detected in both cluster and mosaic form using an analysis of spatial association and a mathematical model that allows discriminating true heterogeneity from artifacts due to the use of thin tissue sections. This study paves the way to evaluate ITH with high accuracy and content while requiring standard staining methods.
Mots-clé
Breast Neoplasms/genetics, Breast Neoplasms/metabolism, Breast Neoplasms/pathology, Cell Line, Tumor, Female, Fluorescent Antibody Technique/methods, Gene Amplification, Gene Expression Regulation, Neoplastic, Genetic Heterogeneity, Humans, In Situ Hybridization, Fluorescence/methods, Microfluidic Analytical Techniques/methods, Receptor, ErbB-2/genetics, Receptor, ErbB-2/metabolism, Reproducibility of Results
Pubmed
Web of science
Création de la notice
29/01/2019 15:52
Dernière modification de la notice
07/07/2020 6:20
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